What Did the Research Show?
- New research indicates that a drug called asciminib (brand name: Scemblix) may be more effective than the current standard of care for patients with newly diagnosed chronic myeloid leukemia (CML).
- The research was presented at this year’s annual American Society of Clinical Oncology (ASCO) conference and showed that asciminib was both more effective and safer than the current standard treatments.
- Asciminib is a type of drug known as a tyrosine kinase inhibitors (TKI) — and researchers compared it to other TKIs currently on the market to evaluate effectiveness and safety.
- Asciminib was already approved by the FDA in October 2021 for patients with chronic-phase CML who had already been treated by two different TKIs (i.e. as a third-line treatment). Novartis, the company that makes the drug, will now apply for approval as a first-line treatment for CML.
The exciting research was presented at this year’s annual American Society of Clinical Oncology (ASCO) conference. Asciminib is a type of drug known as a tyrosine kinase inhibitors (TKI) — and researchers compared it to other TKIs currently on the market to evaluate effectiveness and safety. The research indicated it was both more effective and safer than currently available treatments in patients with newly diagnosed CML. The full results of the ASC4FIRST trial were also published in the New England Journal of Medicine.
Read MoreCML: The Standard of Care
Currently, most patients with CML are treated with one of four different drugs which are all in a class called TKIs. The first TKI was imatinib (Gleevec), which was approved by the Food and Drug Administration (FDA) in 2001. After the introduction of imatinib, the life expectancy of patients with CML improved nearly to that of normal healthy adults, making it one of the most successful targeted cancer drugs of all time. Three second-generation TKIs were also approved for frontline treatment of CML in the following years: nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif). Compared with imatinib, these drugs are more effective with higher response rates and lower rates of disease progression. However, they also tend to have more adverse events (side effects) that can negatively impact a patient’s quality of life and require dose modification.As a result of all of this, many patients with newly diagnosed CML end up having to switch therapies within less than one year of starting treatment. There remains an unmet need for a frontline therapy that is both highly effective and safe — enter asciminib.
What’s the Data on Asciminib?
Asciminib is a BCR-ABL1 inhibitor, which means that it has a different mechanism of action than currently available TKIs. It was intentionally designed to improve effectiveness and decrease side effects compared to imatinib and second-generation TKIs.
Asciminib was already approved by the FDA in October 2021 for patients with chronic-phase CML who had already been treated by two different TKIs (i.e. as a third-line treatment).
The ASC4FIRST trial enrolled adults who had been diagnosed with CML in the three months before enrollment. Enrolled patients could have received up to two weeks of treatment with one of the four previously approved TKIs. Prior to randomization, trial investigators selected a TKI (imatinib or one of the three second-generation TKIs) for each patient based on treatment goals, co-existing medical problems, and patient preferences. Patients were then randomly assigned to receive either the investigator-selected TKI or asciminib.
The primary endpoint for the study was a major molecular response at week 48. This endpoint has previously been shown to be predictive of several important long-term outcomes.
The trial enrolled 405 patients — 201 received asciminib and 204 received an investigator-selected TKI.
Of the 204 patients who received an investigator-selected TKI, 102 received imatinib, 49 received nilotinib, 42 received dasatinib, and 11 received bosutinb. There were approximately 16 months of follow-up time from randomization.
The most important finding of the trial was that Asciminib was substantially more effective than currently available treatments.
A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group vs. 49.0% of patients in the investigator-selected TKI group. Similarly, major molecular response at week 48 was also seen much more frequently in patients initially assigned to imatinib and then randomized to asciminib vs. those receiving just imatinib (69.3% vs. 40.2%).
What About Side Effects?
The side effect profile was also much better for asciminib as well. The rate of grade 3 or higher adverse events was 38.0% for asciminib, which was lower than of Imatinib (44.4%) or second-generation TKIs (54.9%).
Similarly, only 4.5% of patients receiving asciminib had adverse events leading to discontinuation of the trial regimen vs. 11.1% of patients receiving imatinib and 9.8% of patients receiving second-generation TKIs.
The most common side effects observed were:
- Thrombocytopenia (low platelet counts)
- Low white blood cell counts.
Less common side effects included:
- Diarrhea
- Nausea
- Myalgia (muscle pain)
- Muscle spasms
Arterial occlusive events (meaning blood clots in a patient’s arteries) are a significant concern with second-generation TKIs. This occurred in 1% of patients receiving asciminib, 0% receiving imatinib, and 2.0% receiving second-generation TKIs.
Dr. Cortes explained, “There were fewer patients that stopped therapy with Asciminib because of adverse events compared to the other TKIs (about half the incidence). The mechanism of action predicted better selectivity and these results suggest that there is indeed better safety and tolerability than traditional TKIs in this setting.”
One major strength of the ASC4FIRST trial was that the control arm was pragmatic – asciminib was compared to the therapy that doctor’s selected for their patients, as is currently done in clinical practice across the country. Asciminb not only appeared to be safer, but was also more effective.
It is important to emphasize that Asciminib has not received FDA approval yet for use in the frontline setting as it was given in the ASC4FIRST trial. Novartis will be applying for approval in this setting via the FDA’s Real-Time Oncology Review program.
The Future of CML Treatment
Another exciting aspect of this study is the possibility that adoption of asciminib could eventually lead to more patients being candidates for treatment-free remission, meaning they are able to stop active treatment and still remain in remission.
The outcome in this study, major molecular response at week 48, has been shown to be predictive of deep molecular response, which is necessary for treatment-free remission.
Dr. Cortes added, “The early responses have been an increasing focus in recent years and have been shown in many studies to be good predictors of later deep molecular responses. We do need the longer follow-up but I think it is possible we will see many more patients eligible for treatment discontinuation.”
Dr. Cortes also emphasized that close attention to the longer-term follow up from the ASC4FIRST trial will be necessary to understand the long-term effects of asciminib.
“Long-term observation with direct measurement of quality of life will be valuable to assess further the potential benefit of asciminib. We know we have near-normal life expectancy with TKIs… but improvements in quality of life, safety, and treatment free remission are the next frontier that hopefully Asciminib will help address.”
Questions to Ask Your Doctor
- Am I eligible to begin treatment with asciminib?
- What side effects should I be aware of?
- How can we manage common side effects?
- What if I am not able to tolerate the treatment?
- How will I be monitored?
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